Testing the Addition of Duvelisib or CC-486 to the Usual Treatment for Peripheral T-Cell Lymphoma
Purpose
This phase II trial studies the effect of duvelisib or CC-486 and usual chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in treating patients with peripheral T-cell lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as CC-486, cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help find out if this approach is better or worse than the usual approach for treating peripheral T-cell lymphoma.
Conditions
- Angioimmunoblastic T-cell Lymphoma
- Enteropathy-Associated T-Cell Lymphoma
- Follicular T-Cell Lymphoma
- Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
- Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
- Nodal Peripheral T-Cell Lymphoma With TFH Phenotype
- Peripheral T-Cell Lymphoma, Not Otherwise Specified
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) with < 10%
CD30 expression by immunohistochemistry in the following subtypes (by local review):
nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (TFH-PTCL),
follicular T-cell lymphoma, PTCL-not otherwise specified (NOS), angioimmunoblastic
T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma, monomorphic
epitheliotropic intestinal T-cell lymphoma
- Patients with expression of CD30 in >= 10% of the tumor (based on local
immunohistochemistry review) regardless of histology will not be permitted
- Patients with a diagnosis of other PTCL subtype histologies other than those
specified in the inclusion criteria are excluded including large cell
transformation of mycosis fungoides
- Patients will be stratified by presence or absence of TFH phenotype (i.e.
diagnosis of AITL, TFH-PTCL, follicular T-cell lymphoma) based on local review
of pathology. Determination of TFH phenotype can be defined by expression of
two or more of the following markers CD10, BCL6, CXCL13, ICOS, and PD1 by
immunohistochemistry
- Measurable disease as defined by the Lugano criteria
- No prior systemic therapy for lymphoma (excluding corticosteroids)
- Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and
newborn are unknown. Therefore, for women of childbearing potential only, a negative
urine or serum pregnancy test done =< 7 days prior to registration is required
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if secondary to bone marrow
involvement from lymphoma per investigator assessment; the first 12 patients on each
arm of the study must have platelets >= 75,000/mm^3 regardless of bone marrow
involvement)
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or
alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x
upper limit of normal (ULN)
* Except in subjects with documented liver involvement by lymphoma
- Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
- Total bilirubin =< 2.0 x ULN
* Except in cases of Gilbert's Syndrome or documented liver or pancreatic
involvement by lymphoma
- Archival tissue must be available for submission
- Patients known to have HTLV 1/2 are excluded
- Patients with known central nervous system involvement are excluded
- No active viral infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Those who are seropositive (e.g. hepatitis B core antibody [Ab]
positive) are permitted if they are negative by polymerase chain reaction (PCR).
Those who are seropositive for hepatitis B and are negative for hepatitis B virus
(HBV) deoxyribonucleic acid (DNA) by PCR must receive concomitant hepatitis B
directed antiviral therapy. Those who have hepatitis C Ab positivity who have
completed curative therapy for hepatitis C with negative hepatitis C PCR are
eligible
- Patients with history of HIV are eligible if they have an undetectable viral load
for at least 6 months
- No active uncontrolled systemic fungal, bacterial or viral infection (defined as
ongoing signs/symptoms related to the infection without improvement despite
appropriate antibiotics, antiviral therapy and/or other treatment). Patients with
Epstein-Barr virus (EBV) viremia related to their lymphoma are permitted
- No concurrent malignancy requiring active therapy within the last 3 years with the
exception of basal cell carcinoma limited to the skin, squamous cell carcinoma
limited to the skin, carcinoma in situ of the cervix, breast or localized prostate
cancer. Adjuvant hormonal therapy for cancer previously treated for curative intent
is permitted
- Patients must have documented left ventricular ejection fraction of >= 45%
- No significant active cardiac disease within the previous 6 months including:
- New York Heart Association (NYHA) class III or IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention; and/or
- Myocardial infarction
- No contraindication to any drug in the chemotherapy regimen, including neuropathy >=
grade 2
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on
this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14
days prior to registration on the study. Chronic concomitant treatment with strong
CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to
the start of study treatment
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A (duvelisib, CHO[E]P) |
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO QD on days 2-3 for patients =< 60 years old, and prednisone PO QD on days 1-5. Patients also receive duvelisib PO BID on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. |
|
|
Experimental Arm B (CC-486, CHO[E]P) |
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO QD on days 2-3 for patients =< 60 years old, and prednisone PO QD on days 1-5. Patients also receive CC-486 PO QD on days -6 to 0 of cycle -1 and days 8-21 of cycles 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. |
|
|
Active Comparator Arm C (CHO[E]P) |
Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on day 1 or days 1-3 or PO QD on days 2-3 for patients =< 60 years old, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. |
|
Recruiting Locations
Westwood, Kansas 66205
Overland Park, Kansas 66210
More Details
- Status
- Recruiting
- Sponsor
- Alliance for Clinical Trials in Oncology
Detailed Description
PRIMARY OBJECTIVE: I. To compare the complete remission (CR) rates by positron emission tomography (PET)/computed tomography (CT) following completion of treatment with duvelisib-cyclophosphamide (C) doxorubicin (H) vincristine (O) (etoposide [E]) prednisone (P) versus (vs) CHO(E)P and with oral azacitidine (CC-486)-CHO(E)P vs CHO(E)P in previously untreated peripheral T-cell lymphomas that have < 10% expression of CD30. SECONDARY OBJECTIVES: I. To determine the toxicity and tolerability of the treatment regimens. II. To determine the overall response rate (ORR), duration of response, progression free survival (PFS), event free survival (EFS), and overall survival (OS) of each treatment regimen. III. To determine whether designation of follicular helper T-cell phenotype is correlated with response to therapy, PFS, EFS, and OS. IV. To assess the toxicity profile of the experimental regimens in untreated CD30 negative peripheral T-cell lymphomas using Common Terminology Criteria for Adverse Events (CTCAE) and patient reported outcomes (PRO)-CTCAE. OUTLINE: Patients are randomized to 1 of 3 arms. ARM A: Patients receive cyclophosphamide intravenously (IV) on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Patients also receive duvelisib PO twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Patients also receive CC-486 PO QD on days -6 to 0 of cycle -1 and days 8-21 of cycles 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive cyclophosphamide IV on day 1, doxorubicin IV on day 1, vincristine IV on day 1, etoposide IV on days 1-3 or etoposide IV on day 1 and orally (PO) once daily (QD) on days 2-3 for patients <=60 years old, and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 6 weeks after cycle 6 day 1, then every 12 weeks for 2 years, then every 24 weeks until 5 years from end of treatment or until documented progression of lymphoma. After documented progression of lymphoma, patients are followed up every 6 months until 5 years from end of treatment.